Comparative analysis of density histograms and visual scores in incremental and volumetric high-resolution computed tomography of the chest in idiopathic pulmonary fibrosis patients.

BACKGROUND: Volumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management. PURPOSE: To compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT. MATERIAL AND METHODS: Clinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated. RESULTS: Forty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCOsb) was inversely related with the Best score (r = -00.416; p = 0.014), the Kazerooni fibrosis extent (r = -0.481; p = 0.004) and the mean lung attenuation (r = -0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCOsb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique. CONCLUSIONS: Density histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function.

Exercise related ventilation dynamics and clinical correlates in patients with fibrotic idiopathic interstitial pneumonias.

Assessment of exercise performance is a key component in the management of interstitial lung diseases, as its limitation may occur very early. Aim of the present study was to assess ventilation dynamics in combination with pulse-oximetry changes in 54 clinically stable patients affected by idiopathic pulmonary fibrosis or idiopathic fibrotic nonspecific interstitial pneumonia. Testing was successfully performed with the Spiropalm 6-MWT Hand-held spirometer by the majority of cases (94%). End test oxygen saturation (SpO2) values <88% were common in most of patients (76%), with a mean distance walked of 403 meters. Ventilation significantly increased due to the contribution of the tidal volume and the respiratory frequency (RF). This finding was associated with a decrease of the end of test respiratory reserve (RR), that was <20% in 9 cases (17.6%). Lung function was inversely related to the end of test RF, while a positive correlation occurred with the end of test RR and the estimated maximal voluntary ventilation (MVV). RR was also a predictive factor of declining forced vital capacity and lung diffusion capacity for carbon monoxide (DLCO) over a 6-month period. Further factors of DLCO impairment were low SpO2 and MVV. Comparison with the cardio-pulmonary exercise test (CPET) showed that the 6-MWT end of test RR was inversely related to the CPET-derived peak RF and VE/VCO2 suggesting RR as pivotal in exercise limitation assessment. Our results open challenging perspectives in an unexplored field. Future research will include management of latent respiratory failure and monitoring of disease progression and therapy response.

Increased liver stiffness in idiopathic pulmonary fibrosis: a pilot study.

PURPOSE: There is evidence that pulmonary, hepatic and renal fibrosis may share common pathogenetic pathways. Aim of our study was to measure liver stiffness in patients affected by clinically stable idiopathic pulmonary fibrosis (IPF). METHODS: Twenty-nine cases (24 M; mean age±SD: 67±8.3 yrs; 19 ex-smokers) along with fifteen age- and sex-matched healthy volunteers were enrolled. Liver conventional ultrasound examination and transient ultrasound elastography (TUE) were realized by two independent operators. RESULTS: Mild/moderate steatosis was identified in 1 control and 8 IPF cases (6.6% and 27.5%); severe steatosis in 2 IPF patients (7%). Mean TUE measurements were increased in 11 IPF cases (38%) as compared to controls (6.4±2.2 kPa vs 5.2±0.4 kPa; p=0.02). CONCLUSIONS: To our knowledge, this is the first report suggesting that liver stiffness is increased in more than one-third of IPF patients. Application of novel methodologies should be encouraged for investigating further IPF.

Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients.

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-ß and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p<0.001). Conversely, the proportion and absolute number of CD3(+)CD4(+)CD25(high)Foxp-3(+) cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-ß upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-ß/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed.

Genetic screening for LRRK2 gene G2019S mutation in Parkinson's disease patients from Southern Italy.

Leuchine-rich repeat kinase 2 (LRRK2) gene mutations are a common cause of familial and sporadic Parkinson disease (PD). G2019S is the most frequent mutation of the LRRK2 gene and has been reported in about 5-6% of familial and 1-2% of sporadic PD cases. The aim of this study is to investigate the G2019S frequency in a series of 58 familial and 70 sporadic PD patients recruited from Campania, a region in Southern Italy. We identified one heterozygous G2019S mutation in a PD patient who also suffered from obsessive disorder and depression and presented hallucinations and delusional jealousy while he was treated with l-dopa, pramipexole, and amantadine. Brain (18)F-deoxy-glucose PET showed relative decrease of glucose metabolism in the caudate nuclei and to a lesser extent in cortical parietal/frontal regions. The patient's mother also had PD and molecular analysis demonstrated that she carried the same mutation. G2019S mutation frequency is rather low in overall patients (0.8%) and in the familial group (1.7%), suggesting that it may be an uncommon cause of PD in Southern Italy.